Although only a small minority of insects are classified as pests, they nevertheless destroy around 20% of the world's food supply and transmit a diverse array of human and animal pathogens. Control of insect pests is therefore an issue of worldwide agronomic and medical importance. Arthropod pests such as insects have been controlled primarily with chemical insecticides ever since the introduction of DDT in the 1940s. However, control of insect pests in the United States and elsewhere in the world is becoming increasingly complicated for several reasons. First, chemical control subjects the insect population to Darwinian selection and, as a consequence, more than 500 species of arthropods have developed resistance to one or more classes of chemical insecticides. Second, growing awareness of the undesirable environmental and ecological consequences of chemical insecticides, such as toxicity to non-target organisms, has led to revised government regulations that place greater demands on insecticide risk assessment. The loss of entire classes of insecticides due to resistance development or de-registration, combined with more demanding registration requirements for new insecticides, is likely to decrease the pool of effective chemical insecticides in the near future.
Over the past decade, a number of “environmentally friendly” bioinsecticide strategies have been proposed to combat highly resistant insect pests. One recently introduced, and thus far highly successful, approach is the production of transgenic crops that express insecticidal toxins, such as engineered potato, corn, and cotton crops that express delta-endotoxins from the soil bacterium Bacillus thuringiensis. An alternative bioinsecticide strategy that has been successfully field-trialled, and which obviates the problem of introducing a foreign protein into the food supply, is the release of insect-specific viruses that have been engineered to express insecticidal peptide neurotoxins.
A number of investigators have recognized spider venoms as a possible source of insect-specific toxins for agricultural applications. A class of peptide toxins known as the omega-atracotoxins are disclosed in U.S. Pat. No. 5,763,568 as being isolated from Australian funnel-web spiders by screening the venom for “anti-cotton bollworm” activity. One of these compounds, designated omega-ACTX-Hv1a, has been shown to selectively inhibit insect, as opposed to mammalian, voltage-gated calcium channel currents. A second, unrelated family of insect-specific peptidic calcium channel blockers are disclosed as being isolated from the same family of spiders in U.S. Pat. No. 6,583,264.
While several insecticidal peptide toxins isolated from scorpions and spiders appear to be promising leads for the development of insecticides, there still remains a significant need for compounds that act quickly and with high potency against insects, but which display a differential toxicity between insects and vertebrates.